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Vancomycin is often used as antimicrobial prophylaxis for shoulder arthroplasty (SA) either when first generation cephalosporins are contraindicated or colonization with resistant bacteria is anticipated. In general, vancomycin necessitates longer infusion times to mitigate potential side effects. When infusion is started too close to the time of the incision, administration may not be complete during surgery. This study evaluated whether incomplete administration of intravenous (IV) vancomycin prior to shoulder arthroplasty (SA) affects the rate of infectious complications.Between 2000 to 2019, all primary SA types (hemiarthroplasty, anatomic total shoulder arthroplasty, reverse shoulder arthroplasty) performed at a single institution for elective and trauma indications using IV vancomycin as the primary antibiotic prophylaxis and a minimum follow-up of 2 years were identified. The time between the initiation of vancomycin and skin incision was calculated. Complete administration was defined as at least 30 minutes of infusion prior to incision. Demographic characteristics and infectious complications including survival free of prosthetic joint infection (PJI) were generated. Multivariable analyses were conducted to evaluate the association between vancomycin timing and the development of PJI.A total of 461 primary SA were included. Infusion was complete (30 minutes preoperatively) for 163 [35.4%] and incomplete (30 minutes preoperatively) for 298 [64.6%] SA. The incomplete group demonstrated higher rates of any infectious complication (8% vs. 2.3%; P = .005), PJI (5.5% vs. 1%; P = .004), and reoperation inclusive of revision due to infectious complications (4.9% vs. 1%; P = .009). Survivorship free of PJI was worse in SA with incomplete compared to those with complete vancomycin administration. Survival rates for incomplete and complete administration were 97.6% and 99.3% at 1 month, 95.7% and 99.0% at 2 years, 95.1% and 99.0% at 5 years, and 93.9% and 99.0% at 20 years, respectively (P = .006). Multivariable analyses confirmed that incomplete vancomycin administration was an independent risk factor for PJI compared with complete administration (hazard ratio [HR], 4.22 [95% confidence interval (CI), 1.12 to 15.90]; P = .033), even when other independent predictors of PJI (age, male sex, prior surgery, MRSA colonization, and follow-up) were considered.When vancomycin is the primary prophylactic agent used at the time of primary shoulder arthroplasty, incomplete administration (infusion to incision time under 30 minutes) seems to adversely increase the rates of infectious complications and PJI. Prophylaxis protocols should ensure that complete vancomycin administration is achieved to minimize infection after SA.

Background: Healthcare systems are shifting toward “patient-centered” care often without assessing the values important to patients. Analogously, the interests of the patient may be disparate with physician interests, as pay-for-performance models become common. The purpose of the study was to determine which medical preferences are essential for patients during their surgical care. Methods: This prospective, observational study surveyed 102 patients who had undergone a primary knee replacement and/or hip replacement surgery about hypothetical scenarios regarding their surgical experience. Data analysis included categorical variables presented as a number and percent, while continuous variables presented as mean and standard deviation. Statistical analysis for anticoagulation data included the Pearson chi-square test and one-way ANOVA test. Results: A large majority, 73 patients (72%), would not pay to have a four-centimeter or smaller incision. The remaining 29 patients (28%) would prefer to have a four-centimeter or smaller incision and would pay a mean of $1,328 ± 1,629 for that day. A significant number of patients preferred not to use anticoagulation (p = 0.019); however, the value attributed to avoiding a specific method of anticoagulation was found not to be significant (p = 0.507). Conclusions: The study determined the metrics prioritized by hospitals and surgeons are not important to the majority of patients when they evaluate their own care. These disconnects in the entitlements patients expect and receive can be solved by including patients in discussions with physicians and hospital systems.

Purpose: The aim of the study was to determine the restoration of hip biomechanics through lateral offset, leg length, and acetabular component position when comparing non-arthroplasty surgeons (NAS) to elective arthroplasty surgeons (EAS). Methods: 131 patients, with a femoral neck fracture treated with a THA by 7 EAS and 20 NAS, were retrospectively reviewed. 2 blinded observers measured leg-length discrepancy, femoral offset, and acetabular component position. Multivariate logistic regression models examined the association between the surgeon groups and restoration of lateral femoral, acetabular offset, leg length discrepancy, acetabular anteversion, acetabular position, and component size, while adjusting for surgical approach and spinal pathology. Results: NAS under-restored 4.8 mm of lateral femoral offset (43.9 ± 8.7 mm) after THA when compared to the uninjured side (48.7 ± 7.1 mm, p = 0.044). NAS were at risk for under-restoring lateral femoral offset when compared to EAS ( p = 0.040). There was no association between lateral acetabular offset, leg length, acetabular position, or component size and surgeon type. Conclusions: Lateral femoral offset is at risk for under-restoration after THA for femoral neck fractures, when performed by surgeons that do not regularly perform elective THA. This indicates that lateral femoral offset is an under-appreciated contributor to hip instability when performing THA for a femoral neck fracture. Lateral femoral offset deserves as much attention and awareness as acetabular component position since a secondary analysis of our data reveal that preoperative templating and intraoperative imaging did not prevent under-restoration.

Adipose-derived stem cells (ASCs) can be isolated in large quantities from the lipoaspirates of patients. Furthermore, the therapeutic potential of ASCs is vast, with their ability to differentiate into osteogenic, chondrogenic, and adipogenic phenotypes. This chapter focuses on the genetic modifications of ASCs to differentiate into osteogenic cells for bone regeneration. The role of important signaling pathways such as bone morphogenic protein (BMP), hedgehog (HH), and wingless (WNT) are discussed in the context of osteogenesis. Furthermore, the exogenous application of signaling pathway proteins is explored to understand the commitment of stem cells toward osteoblastic differentiation in the setting of cell cultures. The advantages and disadvantages of genetic alteration technologies, including electroporation, viral transduction, minicircles, CRISPR, and nanoparticles, are analyzed to determine methods of promoting osteogenesis by targeting specific genes within the stem cells. Altering the genetic landscape of the innate ASC genome through genetic technologies can establish standardized protocols to safely develop cell-based therapeutics for bone regeneration. Finally, the chapter will highlight ongoing applications of genetically altered ASCs for bone regeneration in patients to establish the current clinical care landscape.

Intermittent pneumatic compression is part of the current standard of care model for preventing venous thromboembolic events (VTE) after total joint arthroplasty. Pneumatic motors limit the rate of inflation resulting in bulky devices with uncomfortable sleeves that inhibited patient compliance and mobility. Nonpneumatic mechanical devices are an alternative for providing mobile, graded, intermittent, sequential, rapid, and monitorable compression posthospitalization. Fifteen healthy volunteers underwent mechanical compression using the Cirvo (Radial Medical, Mountain View, CA) as well as pneumatic compression with four commercially available systems (VenaFlow Elite, Kendall SCD Compression System, ActiveCare DVT, Vasculaire Compression System) and manual calf compression. Peak flow velocity (PFV) was measured by ultrasound of the femoral vein during compression and at baseline. Mechanical compression for 1 second resulted in a significant increase in femoral venous PFV to 107.8 ± 38.2 cm/s from 17.1 ± 4.7 cm/s at baseline (P < .001). The change in femoral venous PFV with mechanical compression for 1 second (90.7 ± 34.9 cm/s) was not statistically different from pneumatic compression from VenaFlow system (106.0 ± 35.6 cm/s, P = .124) and statistically lower than manual calf compression (115.5 ± 26.8 cm/s, P = .015). Pneumatic compression from the VenaFlow system produced the largest change in femoral venous PFV of all commercial pneumatic systems tested. Mechanical compression replicates or exceeds femoral venous PFV available from currently available intermittent pneumatic compression.

Background Bone retains regenerative potential into adulthood, and surgeons harness this plasticity during distraction osteogenesis. The underlying biology governing bone development, repair, and regeneration is divergent between the craniofacial and appendicular skeleton. Each type of bone formation is characterized by unique molecular signaling and cellular behavior. Recent discoveries have elucidated the cellular and genetic processes underlying skeletal development and regeneration, providing an opportunity to couple biological and clinical knowledge to improve patient care. Methods A comprehensive literature review of basic and clinical literature regarding craniofacial and long bone development, regeneration, and distraction osteogenesis was performed. Results The current understanding in craniofacial and long bone development and regeneration is discussed, and clinical considerations for the respective distraction osteogenesis procedures are presented. Conclusions Distraction osteogenesis is a powerful tool to regenerate bone and thus address a number of craniofacial and appendicular skeletal deficiencies. The molecular mechanisms underlying bone regeneration, however, remain elusive. Recent work has determined that embryologic morphogen gradients constitute important signals during regeneration. In addition, striking discoveries have illuminated the cellular processes underlying mandibular regeneration during distraction osteogenesis, showing that skeletal stem cells reactivate embryologic neural crest transcriptomic processes to carry out bone formation during regeneration. Furthermore, innovative adjuvant therapies to complement distraction osteogenesis use biological processes active in embryogenesis and regeneration. Additional research is needed to further characterize the underlying cellular mechanisms responsible for improved bone formation through adjuvant therapies and the role skeletal stem cells play during regeneration.

Background Piriformis-sparing approaches to the hip allow surgeons to avoid releasing the piriformis tendon during total hip arthroplasty; however, the consequences of retracting an intact piriformis tendon during such an approach remain ill-defined. The present study aimed to determine the upper limit of force that can be applied during retraction of the piriformis tendon to expose the hip, and to quantify the resultant damage to the piriformis musculotendinous complex. Methods A patent-pending instrumented retractor was designed to record the applied force, duration, and angle of retraction during a piriformis-sparing posterior approach to the hip. In addition to the data collected with use of the instrumented retractor, damage to the piriformis muscle and tendon was quantified by a blinded observer. Results There was no damage to the piriformis tendon in 22 (96%) of 23 hips during piriformis retraction for visualization of the hip capsule; however, there was complete or partial damage to the piriformis muscle at the sacral origin, belly, or musculotendinous junction (i.e., outside the surgical field) noted in 21 (91%) of 23 hips. The mean peak force to failure of the piriformis muscle was exceedingly small (29.0 ± 9.4 N; range, 10.1 to 44.9 N). Conclusions The mean peak force applied to the piriformis retractor is much less than the force required for several common daily activities, such as opening a door or crushing an empty aluminum can. Soft-tissue damage that occurs outside the surgical field during the retraction of unreleased muscles, like the piriformis muscle, is common and remains an uncontrolled surgical variable. This inadvertent soft-tissue damage is not routinely accounted for when accessing the invasiveness of a procedure. Hence, it is no longer adequate to define a minimally invasive surgical procedure simply as an approach that involves the limited release of anatomical structures. Clinical relevance The use of instrumented retractors may redefine surgical invasiveness by providing data that could alter our understanding of the soft-tissue damage caused by retraction and open the possibility of robot-assisted or damage-limiting retractor systems.

Bone development occurs through a series of synchronous events that result in the formation of the body scaffold. The repair potential of bone and its surrounding microenvironment — including inflammatory, endothelial and Schwann cells — persists throughout adulthood, enabling restoration of tissue to its homeostatic functional state. The isolation of a single skeletal stem cell population through cell surface markers and the development of single-cell technologies are enabling precise elucidation of cellular activity and fate during bone repair by providing key insights into the mechanisms that maintain and regenerate bone during homeostasis and repair. Increased understanding of bone development, as well as normal and aberrant bone repair, has important therapeutic implications for the treatment of bone disease and ageing-related degeneration. This Review discusses the cell types, critical genes and transcription factors involved in bone development and repair. The dysfunctional cellular and molecular signalling that results in clinical bone disease is also outlined, thus informing the current state of science and clinical practice.

Background Prior data demonstrate significant heterogeneity regarding coronary artery disease risk factors and outcomes among Asians in the United States, but no studies have yet examined coronary artery disease treatment patterns or outcomes among disaggregated Asian American subgroups. Methods and Results From a total of 772 882 patients with known race/ethnicity and sex who received care from a mixed‐payer healthcare organization in Northern California between 2006 and 2015, a retrospective analysis was conducted on 6667 adults with coronary artery disease. Logistic regression was used to examine medical and procedural therapies and outcomes by race/ethnicity, with adjustment for age, sex, income, and baseline comorbidities. Compared with non‐Hispanic whites, Chinese were more likely to undergo stenting (50.9% versus 60.8%, odds ratio [ OR ] 1.39 [95% CI , 1.04–1.87], p=0.005), whereas Filipinos were more likely to receive bypass surgery (6.9% versus 20.5%, OR 2.65 [95% CI , 1.75–4.01], P OR s 1.86 [95% CI , 1.13–3.04], 1.86 [95% CI , 1.01–3.44], and 4.37 [95% CI , 1.02–18.67], respectively, P OR s 1.49 [95% CI , 1.02–2.19] and 1.68 [95% CI , 1.21–2.34], respectively, P Conclusions Disaggregation of Asian Americans with coronary artery disease into individual racial/ethnic subgroups reveals significant variability in treatment patterns and outcomes. Further investigation into these differences may expose important opportunities to mitigate disparities and improve quality of care in this diverse population.

Summary: Regenerative paradigms exhibit nerve dependency, including regeneration of the mouse digit tip and salamander limb. Denervation impairs regeneration and produces morphological aberrancy in these contexts, but the direct effect of innervation on the stem and progenitor cells enacting these processes is unknown. We devised a model to examine nerve dependency of the mouse skeletal stem cell (mSSC), the progenitor responsible for skeletal development and repair. We show that after inferior alveolar denervation, mandibular bone repair is compromised because of functional defects in mSSCs. We present mSSC reliance on paracrine factors secreted by Schwann cells as the underlying mechanism, with partial rescue of the denervated phenotype by Schwann cell transplantation and by Schwann-derived growth factors. This work sheds light on the nerve dependency of mSSCs and has implications for clinical treatment of mandibular defects. : Jones et al. demonstrate the nerve dependency of mandibular bone repair after degeneration of the inferior alveolar nerve. Schwann cell paracrine signaling is required for skeletal stem cell enactment of bone healing. Rescue of healing by Schwann cell transplantation highlights skeletal stem cell-Schwann cell circuitry during mandibular repair. Keywords: skeletal stem cells, Schwann cells, mandibular repair, nerve-dependent mandibular regeneration

Background Nutrition is believed to be a primary contributor in regulating gene expression by affecting epigenetic pathways such as DNA methylation and histone modification. Resveratrol and pterostilbene are phytoalexins produced by plants as part of their defense system. These two bioactive compounds when used alone have been shown to alter genetic and epigenetic profiles of tumor cells, but the concentrations employed in various studies often far exceed physiologically achievable doses. Triple-negative breast cancer (TNBC) is an often fatal condition that may be prevented or treated through novel dietary-based approaches. Methods HCC1806 and MDA-MB-157 breast cancer cells were used as TNBC cell lines in this study. MCF10A cells were used as control breast epithelial cells to determine the safety of this dietary regimen. CompuSyn software was used to determine the combination index (CI) for drug combinations. Results Combinatorial resveratrol and pterostilbene administered at close to physiologically relevant doses resulted in synergistic (CI

SUMMARY Microdeletions involving TBX1 result in variable congenital malformations known collectively as 22q11.2 deletion syndrome (22q11.2DS). Tbx1-deficient mice and zebrafish recapitulate several disease phenotypes, including pharyngeal arch artery (PAA), head muscle (HM), and cardiac outflow tract (OFT) deficiencies. In zebrafish, these structures arise from nkx2.5+ progenitors in pharyngeal arches 2–6. Because pharyngeal arch morphogenesis is compromised in Tbx1-deficient animals, the malformations were considered secondary. Here, we report that the PAA, HM, and OFT phenotypes in tbx1 mutant zebrafish are primary and arise prior to pharyngeal arch morphogenesis from failed specification of the nkx2.5+ pharyngeal lineage. Through in situ analysis and lineage tracing, we reveal that nkx2.5 and tbx1 are co-expressed in this progenitor population. Furthermore, we present evidence suggesting that gdf3-ALK4 signaling is a downstream mediator of nkx2.5+ pharyngeal lineage specification. Collectively, these studies support a cellular mechanism potentially underlying the cardiovascular and cranio-facial defects observed in the 22q11.2DS population., In Brief Microdeletions encompassing the TBX1 locus cause 22q11.2 deletion syndrome (DS), which is characterized by congenital heart, aorta, and craniofacial malformations. Using a zebrafish model of 22q11.2DS, Guner-Ataman et al. demonstrate that tbx1-mutant animals fail to specify the nkx2.5+ progenitor population that gives rise to the affected structures., Graphical Abstract